Simulating therapeutic drug monitoring results for dose individualisation to maintain investigator blinding in a randomised controlled trial
| dc.contributor.author | Lesosky, Maia | |
| dc.contributor.author | Joska, John | |
| dc.contributor.author | Decloedt, Eric | |
| dc.date.accessioned | 2017-06-13T06:50:10Z | |
| dc.date.available | 2017-06-13T06:50:10Z | |
| dc.date.issued | 2017-06-07 | |
| dc.date.updated | 2017-06-11T03:15:01Z | |
| dc.description.abstract | Background: Therapeutic drug monitoring (TDM) is essential practice when dosing drugs with a narrow therapeutic index in order to achieve a plasma drug concentration within a narrow target range above the efficacy concentration but below the toxicity concentration. However, TDM with dose individualisation is challenging during a double-blind clinical trial with laboratory staff and investigators blinded to treatment arm allocation. Methods: Drug concentrations were simulated for participants in the placebo arm by an unblinded independent statistician, utilising the measured values from the treatment arm participants. Simulated and actual concentrations were re-blinded and passed on to a dose-adjusting investigator, who made dose adjustment recommendations but was not directly responsible for clinical care of participants. Results: A total of 257 sham lithium plasma concentrations were simulated utilising 242 true lithium plasma concentrations in real time as the trial progressed. The simulated values had a median (interquartile range) of 0.59 (0.46, 0.72) compared to 0.53 (0.39, 0.72) in the treatment arm. Blinding of the laboratory staff and dose-adjusting investigator was maintained successfully. Conclusions: We succeeded in simulating sham lithium plasma concentrations while maintaining blinding. Our simulated values have a smaller range than the observed data, which can be explained by the challenges with respect to drug adherence and dose timing that were experienced. Trial registration: Pan African Clinical Trials Registry, PACTR201310000635418. Registered on 30 August 2013. | |
| dc.identifier.apacitation | Lesosky, M., Joska, J., & Decloedt, E. (2017). Simulating therapeutic drug monitoring results for dose individualisation to maintain investigator blinding in a randomised controlled trial. <i>Trials</i>, http://hdl.handle.net/11427/24567 | en_ZA |
| dc.identifier.chicagocitation | Lesosky, Maia, John Joska, and Eric Decloedt "Simulating therapeutic drug monitoring results for dose individualisation to maintain investigator blinding in a randomised controlled trial." <i>Trials</i> (2017) http://hdl.handle.net/11427/24567 | en_ZA |
| dc.identifier.citation | Lesosky, M., Joska, J., & Decloedt, E. (2017). Simulating therapeutic drug monitoring results for dose individualisation to maintain investigator blinding in a randomised controlled trial. Trials, 18(1), 261. | |
| dc.identifier.ris | TY - Journal Article AU - Lesosky, Maia AU - Joska, John AU - Decloedt, Eric AB - Background: Therapeutic drug monitoring (TDM) is essential practice when dosing drugs with a narrow therapeutic index in order to achieve a plasma drug concentration within a narrow target range above the efficacy concentration but below the toxicity concentration. However, TDM with dose individualisation is challenging during a double-blind clinical trial with laboratory staff and investigators blinded to treatment arm allocation. Methods: Drug concentrations were simulated for participants in the placebo arm by an unblinded independent statistician, utilising the measured values from the treatment arm participants. Simulated and actual concentrations were re-blinded and passed on to a dose-adjusting investigator, who made dose adjustment recommendations but was not directly responsible for clinical care of participants. Results: A total of 257 sham lithium plasma concentrations were simulated utilising 242 true lithium plasma concentrations in real time as the trial progressed. The simulated values had a median (interquartile range) of 0.59 (0.46, 0.72) compared to 0.53 (0.39, 0.72) in the treatment arm. Blinding of the laboratory staff and dose-adjusting investigator was maintained successfully. Conclusions: We succeeded in simulating sham lithium plasma concentrations while maintaining blinding. Our simulated values have a smaller range than the observed data, which can be explained by the challenges with respect to drug adherence and dose timing that were experienced. Trial registration: Pan African Clinical Trials Registry, PACTR201310000635418. Registered on 30 August 2013. DA - 2017-06-07 DB - OpenUCT DO - 10.1186/s13063-017-1992-6 DP - University of Cape Town J1 - Trials LK - https://open.uct.ac.za PB - University of Cape Town PY - 2017 T1 - Simulating therapeutic drug monitoring results for dose individualisation to maintain investigator blinding in a randomised controlled trial TI - Simulating therapeutic drug monitoring results for dose individualisation to maintain investigator blinding in a randomised controlled trial UR - http://hdl.handle.net/11427/24567 ER - | en_ZA |
| dc.identifier.uri | http://dx.doi.org/10.1186/s13063-017-1992-6 | |
| dc.identifier.uri | http://hdl.handle.net/11427/24567 | |
| dc.identifier.vancouvercitation | Lesosky M, Joska J, Decloedt E. Simulating therapeutic drug monitoring results for dose individualisation to maintain investigator blinding in a randomised controlled trial. Trials. 2017; http://hdl.handle.net/11427/24567. | en_ZA |
| dc.language.iso | en | |
| dc.publisher | BioMed Central | |
| dc.publisher.department | Department of Public Health and Family Medicine | en_ZA |
| dc.publisher.faculty | Faculty of Health Sciences | en_ZA |
| dc.publisher.institution | University of Cape Town | |
| dc.rights.holder | The Author(s). | |
| dc.source | Trials | |
| dc.source.uri | https://trialsjournal.biomedcentral.com/ | |
| dc.subject.other | Dose adjustment | |
| dc.subject.other | Blinding | |
| dc.subject.other | Simulation | |
| dc.title | Simulating therapeutic drug monitoring results for dose individualisation to maintain investigator blinding in a randomised controlled trial | |
| dc.type | Journal Article | |
| uct.type.filetype | Text | |
| uct.type.filetype | Image | |
| uct.type.publication | Research | en_ZA |
| uct.type.resource | Article | en_ZA |